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Evolution of the partial thromboplastin time (PTT) ratio and antiphospholipid syndrome involve ment during the course of melanoma. The number of months from initial diagnosis of melanoma is indicated. Black arrows (↓) indicate the six injections of vaccine, while pegylated interferon-alpha-2b was given every week (1.5 μg/week/kg) from time of inclusion. Diamonds : PTT value; stars : detected lupus anticoagulant; grey histograms : anticardiolipin immunoglobulin G antibodies titres (IU/l) detected by enzyme-linked immunosorbent assay.
Source publication
Immunotherapeutic approaches have been developed recently for the treatment of advanced melanoma, based on the finding that the immunological response to mela-noma plays a key role in control of the disease (1). We report here a case of a patient with metastatic melanoma who developed antiphospholipid syndrome (APLS) after initiation of immunothera...
Context in source publication
Context 1
... patient received six subcutaneous injections of mature dendritic cells pulsed with lysates of three me- lanoma cell lines from 3 August to 11 October 2006, followed by subcutaneous pegylated interferon-alpha- 2b (PEG-IFNα 2b) (1.5 µg/kg/week) from 5 August to 15 November 2006 ( Fig. 1). In October 2006, a new CT scan revealed bilateral enlargement of lymph nodes in the iliac and inguinal areas, but lymphadenectomy showed no metastasis. Six days later, cyanotic and hype- raesthesic lesions appeared on the first left toe, followed by spreading of bilateral purpuric, necrotic areas and erythematous, purple painful ...
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The presence of autoantibodies against immunoregulatory effectors can be relevant for onset and/or progression of autoimmune disease. Emerging insights into immunological activity profile including a role as opsonins give reason to systematically monitor sera of patients for immunoglobulin G autoantibodies, preferably for several galectins at the s...
Citations
... La isquemia digital grave puede ser la forma de presentación del SAF en pacientes con cáncer 4 e incluso se ha notificado en enfermos tratados con inmunoterapia [10][11][12] . Por ello, si bien este tipo de lesiones no forman parte de los criterios de clasificación del SAF deberían hacer sospechar la enfermedad 13 . ...
... La isquemia digital grave puede ser la forma de presentación del SAF en pacientes con cáncer 4 e incluso se ha notificado en enfermos tratados con inmunoterapia [10][11][12] . Por ello, si bien este tipo de lesiones no forman parte de los criterios de clasificación del SAF deberían hacer sospechar la enfermedad 13 . ...
The present case corresponds to a woman with history of three miscarrieges less than10 weeks and breast cancer, who develops severe digital ischemia after the second cycle of capecitabine. Positive antiphospholipid antibodies were determined. Patients with obstetric antiphospholipid syndrome have an increased risk of developing cancer, and severe digital ischemia could be an unusual form of presentation of the antiphospholipid syndrome in patients with cancer. This case is presented to highlight the benefit of researching and making an early diagnosis of these characteristics of the disease.
... It is postulated that the autoantibodies may be a direct consequence of the tumour itself [39,40] or it also could be the reason of specific cancer therapies [41]. For instance, while treating different types of malignancies with chemotherapies [42,43] and immunotherapies [44,45], APS was observed to developed. Several mechanisms have been suggested to explain the association between aPLs and cancer including (i) production of autoantibodies as a response to tumour antigens; (ii) secretion of aCL antibodies from tumour cells; and (iii) production of monoclonal immunoglobulins with LA and aCL activities [46]. ...
Antiphospholipid antibodies (aPLs) are autoantibodies with laboratory significance in developing thrombosis and pregnancy morbidity in antiphospholipid syndrome (APS). High prevalence of aPLs namely - anticardiolipin, anti-β2-glycoprotein I, lupus anticoagulant, antiphosphatidylcholine, antiphosphatidylserine, antiphosphatidylinositol,
antiphosphatidylethanolamine and antiprothrombin antibodies have been observed in patients with different types of haematological malignancies and solid tumours. Although cancer patients have high risk of developing thrombosis, the risk becomes even higher in aPLs carriers. Although the relationship between aPLs and cancer has to be further investigated, however, the presence of aPLs in neoplastic patients can possibly increase the risk of developing thrombosis.
As the pathogenic role of aPLs in cancer is still a matter of debate, more researches should be conducted on the association between the aPLs and malignancies towards the potential impact on understanding the pathogenicity and treatment when cancer and APS coexists.
... Also, some patients with monoclonal gammopathies may secrete immunoglobulins with aCL activity. 30,46,[74][75][76][77] Finally, the potential effect of cancer therapy is not well understood, but in the new era of immunotherapy, development of autoimmune antibodies is considered part of the spectrum of immune-related adverse events. Studies have shown that polymorphism mucin-like molecules such as P-selectin may contribute to the thrombotic risk of aPL. ...
This review summarizes the evidence on antiphospholipid (aPL) antibodies and related thromboembolic events in patients with solid tumors. Data sources included Medline, EMBASE, Web of Science, PubMed ePubs, and the Cochrane Central Register of Controlled Trials through August 2019 without restrictions. Observational studies that evaluated patients with solid tumors for the presence of aPL antibodies were included. Data were extracted and quality was assessed by one reviewer and cross-checked by another. Thirty-three studies were identified. Gastrointestinal (GI) and genitourinary (GU) cancers were the most frequently reported. Compared with healthy patients, patients with GI cancer were more likely to develop anticardiolipin antibodies (risk ratio [RR], 5.1; 95% confidence interval [CI], 2.6-9.95), as were those with GU (RR, 7.3; 95% CI, 3.3-16.2) and lung cancer (RR, 5.2; 95% CI, 1.3-20.6). The increased risk for anti-β2-glycoprotein I or lupus anticoagulant was not statistically significant. Patients with lung cancer who had positive aPL antibodies had higher risk of developing thromboembolic events than those who had negative antibodies (RR, 3.8%; 95% CI, 1.2-12.2), while the increased risk in patients with GU cancer was not statistically significant. Deaths due to thromboembolic events were more common among patients with lung cancer who had elevated aPL antibodies. A limitation of this review is that the results are contingent on the reported information. We found an increased risk of developing aPL antibodies in patients with GI, GU, and lung cancers resulting in thromboembolic events and death. Further studies are needed to better understand the pathogenesis and development of aPL antibodies in cancer.
... APLS can also occur secondary to infections, malignancy, and drugs such as hydralazine, isoniazid, and quinine [9]. Previous immune therapies for melanoma, including interferon and dendritic cell/melanoma cell line infusions, have been reported to cause APLS [10,11]. In a review of all cases of malignancies associated with APL antibodies, melanoma was reported in 5% [11]. ...
... Previous immune therapies for melanoma, including interferon and dendritic cell/melanoma cell line infusions, have been reported to cause APLS [10,11]. In a review of all cases of malignancies associated with APL antibodies, melanoma was reported in 5% [11]. Although 'paraneoplastic' APLS is a consideration, the temporal relationship of development of APLS with a known immunostimulant (combined immunotherapy) makes it likely that it played a major role in the development of APLS in this patient. ...
... [48] One might even speculate about a possible role of type I IFNs in promoting antiphospholipid antibody formation given numerous reports of iatrogenic APS in patients treated with IFN-α for hepatitis C and melanoma. [49][50][51] A limitation of our study is that while our APS patient cohorts are well-characterized for standard clinical variables, we do not have data regarding endothelial function/dysfunction for the patients recruited into this study. Follow-up work will explore the EPC/CAC defect, as well as type I IFN expression, in a cohort where such data are available. ...
Objectives:
Patients with antiphospholipid syndrome (APS) are at risk for subclinical endothelial injury, as well as accelerated atherosclerosis. In the related disease systemic lupus erythematosus, there is a well-established defect in circulating endothelial progenitors, which leads to an accrual of endothelial damage over time. This defect has been at least partially attributed to exaggerated expression of type I interferons (IFNs). We sought to determine whether these pathways are important in APS.
Methods:
We studied 68 patients with primary APS. Endothelial progenitors were assessed by flow cytometry and functional assay. Type I IFN activity was determined by a well-accepted bioassay, while peripheral blood mononuclear cells were scored for expression of IFN-responsive genes.
Results:
Endothelial progenitors from patients with APS demonstrated a marked defect in the ability to differentiate into endothelial cells, a phenotype which could be mimicked by treating control progenitors with APS sera. Elevated type I IFN activity was detected in the circulation of patients with APS (a finding that was then replicated in an independent cohort). While IgG depletion from APS sera did not rescue endothelial progenitor function, the dysfunction was successfully reversed by a type I IFN receptor-neutralising antibody.
Conclusions:
We describe, for the first time to our knowledge, an IFN signature in primary APS and show that this promotes impaired endothelial progenitor function. This work opens the door to novel approaches that may mitigate vascular damage in APS, such as anti-IFN drugs.
